PROJECT SUMMARY Dopamine, norepinephrine, and serotonin are major modulatory neurotransmitters that are implicated in a wide variety of psychiatric and neurological disorders, including addiction. Current available methods to quantify the dynamics of these neurotransmitters in extracellular space are not as fast, sensitive, direct or do not have the requisite spatial and temporal resolution. In specific aim 1, I present results from recent progress I have made in synthesis of a fluorescent probe for dopamine. Using mice acute brain slice preparations, I show that the near-infrared emitting nanoscale probe can capture the fast dynamics of dopamine release and clearance from the extracellular space at spatial scales that have heretofore been inaccessible. I present results that show imaging of dopamine dynamics in the dorsal striatum as well as the prefrontal cortex. In specific aim 2, I propose to use this nanoprobe for the interrogation of aberrations in dopamine signaling in Parkinson's disease mice models. In specific aim 3, I provide a postdoctoral research proposal in which I seek to expand my current skill sets through in vivo dopamine imaging and acquire new skill sets to start an independent research career in the development and application of novel probes for studying the extracellular dynamics and downstream cellular biochemical steps of the modulatory monoamine neurotransmitters.